Cell-to-cell modeling of the interface between atrial and sinoatrial anisotropic heterogeneous nets.

The transition between sinoatrial cells and atrial cells in the heart is not fully understood. Here we focus on cell-to-cell mathematical models involving typical sinoatrial cells and atrial cells connected with experimentally observed conductance values. We are interested mainly in the geometry of the microstructure of the conduction paths in the sinoatrial node. We show with some models that appropriate source-sink relationships between atrial and sinoatrial cells may occur according to certain geometric arrangements.

Obesity and perioperative complications in head and neck free tissue reconstruction.

BACKGROUND: Free tissue transfer is a mainstay in reconstruction of complex head and neck defects. The purpose of this study was to determine if perioperative complications were more common in patients with body mass index (BMI) >30 kg/m(2) undergoing free flap reconstruction. METHODS: A multi-institutional retrospective cohort was created. Medical complications, surgical complications, and procedural variables were recorded. Logistic regression was used to investigate univariate and multivariate associations between outcomes and predictors. RESULTS: Of 582 cases, 128 patients (22%) had BMI >30. Surgical complications occurred in 153 cases (26.3%), with an adjusted odds ratio (OR) for association of surgical complications with BMI >30 of 0.92 (p = .71). Medical complications occurred in 178 cases (30.6%), with an adjusted OR of 0.78 (p = .26). Age and advanced comorbidity status (Adult Comorbidity Evaluation-27 [ACE-27] 2 or 3) were associated with medical complications (p < .0001). CONCLUSION: BMI >30 does not predict medical or surgical complications in patients undergoing head and neck free flap surgery. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1188-E1191, 2016.

Interferon regulatory factor 6 promotes differentiation of the periderm by activating expression of Grainyhead-like 3.

IFN regulatory factor 6 (IRF6) is a transcription factor that, in mammals, is required for the differentiation of skin, breast epithelium, and oral epithelium. However, the transcriptional targets that mediate these effects are currently unknown. In zebrafish and frog embryos, Irf6 is necessary for differentiation of the embryonic superficial epithelium, or periderm. Here we use microarrays to identify genes that are expressed in the zebrafish periderm and whose expression is inhibited by a dominant-negative variant of Irf6 (dnIrf6). These methods identify Grainyhead-like 3 (Grhl3), an ancient regulator of the epidermal permeability barrier, as acting downstream of Irf6. In human keratinocytes, IRF6 binds conserved elements near the GRHL3 [corrected] promoter. We show that one of these elements has enhancer activity in human keratinocytes and zebrafish periderm, suggesting that Irf6 directly stimulates Grhl3 expression in these tissues. Simultaneous inhibition of grhl1 and grhl3 disrupts periderm differentiation in zebrafish, and, intriguingly, forced grhl3 expression restores periderm markers in both zebrafish injected with dnIrf6 and frog embryos depleted of Irf6. Finally, in Irf6-deficient mouse embryos, Grhl3 expression in the periderm and oral epithelium is virtually absent. These results indicate that Grhl3 is a key effector of Irf6 in periderm differentiation.

S-Adenosylhomocysteine hydrolase of the protozoan parasite Trichomonas vaginalis: potent inhibitory activity of 9-(2-deoxy-2-fluoro-ß,D-arabinofuranosyl)adenine.

In the present study, we carried out a structure-activity analysis in Trichomonas vaginalis of a series of adenosine and uridine analogues. The most potent compounds were found to be 2' and 3' modified adenosine analogues some of which are potent inhibitors of S-adenosylhomocysteine hydrolase. The 9-(2-deoxy-2-fluoro-ß,D-arabinofuranosyl)adenine compound was more potent than metronidazole, a current FDA approved and commonly prescribed drug for treatment of trichomoniasis. Its IC(50) was 0.09 µM compared to 0.72 µM for metronidazole.

Pneumocephalus with BiPAP use after transsphenoidal surgery.

While the benefits of continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) for patients with obstructive sleep apnea are well described, reports in the literature of complications from its use are rare. A patient who received postoperative BiPAP after undergoing transsphenoidal craniopharyngioma resection developed severe pneumocephalus and unplanned intensive care unit admission. Although the pneumocephalus resolved with conservative management over two weeks, we propose caution in the use of CPAP postoperatively in patients undergoing procedures of the head and neck.

Theraputic targeting of Trk supresses tumor proliferation and enhances cisplatin activity in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) is a biologically aggressive disease that has been modestly impacted by improvements in therapeutic strategies. Several lines of evidence support the role of TrkB for invasion and metastasis in various solid tumor models, and we have shown an important function of this receptor in HNSCC tumor biology. Therapeutic modulation of TrkB function has been supported in the literature by the development of small molecule inhibitors (SMI) with minimal success. To assess the validity of targeting TrkB in HNSCC, we tested a novel agent, AZ64 and show significant dose and time-dependent inhibition of cellular proliferation in cell lines. Genetic studies revealed the specificity of this compound for the TrkB receptor, as exposure of cells that had genetic suppression of TrkB did not demonstrate abrogated oncogenic signaling. We next assessed the impact of AZ64 as a chemotherapy-sensitizer and identified an enhancement of cisplatin-mediated anti-proliferation across all cell lines. We then demonstrated that AZ64 can overcome chemotherapy resistance in a novel model of cisplatin resistance in HNSCC. Modulation of the pro-oncogenic STAT3 and Src pathways was identified, suggesting molecular mechanisms of action for AZ64. In this study, we demonstrate the feasibility of targeting TrkB and suggest a novel approach for the treatment of some chemotherapy-resistant HNSCC.

Outcomes of pediatric patients with malignancies of the major salivary glands.

BACKGROUND: To report the outcomes and early to long term treatment complications among pediatric patients with major salivary gland malignancies treated at a single institution. MATERIALS AND METHOD: This study was a retrospective case review set at a tertiary referral cancer center. Patients less than 19 years of age with a diagnosis of a major salivary gland malignancy were identified at the M. D. Anderson tumor database between 1953 and 2006. RESULTS: A total of 61 patients were identified, with equal gender distribution. The majority of tumors arose in the parotid gland (83%), and the most common pathology was mucoepidermoid carcinoma (46%). Lymphatic metastasis was identified in 37% of patients, nearly all with mucoepidermoid carcinoma. Although 65% of patients had prior treatment elsewhere, more than 75% of patients underwent surgical resection at our institution. External beam radiation was used in 45% of patients, with an average dose of 58.6 Gray. Average patient follow-up was 153 months. The overall survival rate was 93% at 5 years, and 26% developed a recurrence. A second primary was identified in 2 patients. Permanent facial paresis was noted in 7 patients (12%) and xerostomia in 1 patient (4%). CONCLUSIONS: Survival of pediatric patients with major salivary gland carcinomas is favorable. Adverse outcomes were best predicted by tumor grade, margin status, and neural involvement. Radiation therapy is beneficial for locoregional control of disease, with acceptable long-term treatment sequelae, and without a significant risk for developing second primary tumors. Survivorship issues need to be addressed in this patient population into adulthood.